Pluripotent Very Small Embryonic-Like Stem Cells in Adult Testes – An Alternate Premise to Explain Testicular Germ Cell Tumors

2018 ◽  
Vol 14 (6) ◽  
pp. 793-800 ◽  
Author(s):  
Ankita Kaushik ◽  
Deepa Bhartiya
Keyword(s):  
Stem Cells ◽  
Germ Cell ◽  
Germ Cell Tumors ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell

Immunohistochemical expression of cancer stem cell markers OCT3/4, NANOG, DPPA4, and CCND2 in testicular germ cell tumors.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 333-333 ◽  
Author(s):  
Ravendra Ryan Moniz ◽  
Walter Henriques Costa ◽  
Victor Soares Fanni ◽  
Isabela Werneck Cunha ◽  
Rafael Malagoli Rocha ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Germ Cell ◽  
Germ Cell Tumors ◽  
Stem Cell Markers ◽  
Testicular Germ Cell Tumors ◽  
Immunohistochemical Expression ◽  
Testicular Germ Cell ◽  
Cell Markers ◽  
Cancer Stem Cell Markers

333 Background: The purpose of this study was to examine the immunohistochemical expression of OCT3/4, CCND2, DPPA4 and NANOG in primary non-seminomatous germ cell testicular tumors that might be associated with different entities of germ cell tumors. OCT3/4, NANOG, DPPA4 and CCND2 have been identified as key regulators of pluripotency in mammalian embryonic and induced stem cells. Methods: Tissue samples of non seminoma testicular germ cell tumors including carcinoma in situ (CIS, n=10), seminoma component (n=5), embryonic carcinoma (n=20), mature teratoma (n= 7), immature teratoma (n=7), yolk sac tumor (n=5) and choriocarcinoma (n=3) were first analyzed by histological evaluation followed by selection of the appropriate tissue sections prepared from paraffin embedded testicular tissue blocks fixed with buffered formalin. To investigate immunohistochemical expression, of cancer stem cell markers samples tissues were analyzed under central pathological evaluation. Results: In CIS cells all markers were detected with a strong immunohistochemical expression suggesting that CIS cells maintain characteristics of embryonic stem cells. The invasive tumor samples, in comparison, showed a more heterogeneous expression pattern of OCT3/4, NANOG, DPPA4 and CCND2. There was an abundant expression in seminomas and embryonic carcinomas compared to a marked reduction expression in choriocarcinoma and teratomas. The expression of the markers was related to tumoral tissue differentiation. The seminomatous component and the embryonic carcinoma and undifferentiated tissues such as intratubular neoplasia presented elevated expressions. Specialized tissues such as teratoma and choriocarcinoma present low expression levels or absence of studied markers. The teratomatous subtypes do not express NANOG. The sub-type coriocarcinoma tumors do not express CCND2 and NANOG. Conclusions: The immunohistochemical expression of stem cell markers OCT3/4, NANOG, DPPA4 and CCND2 follow a specific pattern that is related to tumoral differentiation and consequent loss of pluripotency characteristics.

scholarly journals Targeting Cancer Stem Cells with Differentiation Agents as an Alternative to Genotoxic Chemotherapy for the Treatment of Malignant Testicular Germ Cell Tumors

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2045
Author(s):  
Amanda R. Loehr ◽  
Timothy M. Pierpont ◽  
Eric Gelsleichter ◽  
Anabella Maria D. Galang ◽  
Irma R. Fernandez ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Germ Cell ◽  
Germ Cell Tumors ◽  
Xenograft Model ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell ◽  
Significant Toxicity ◽  
Ec Cells

Testicular germ cell tumors (TGCTs) are exceptionally sensitive to genotoxic chemotherapy, resulting in a high cure rate for the young men presenting with these malignancies. However, this treatment is associated with significant toxicity, and a subset of malignant TGCTs demonstrate chemoresistance. Mixed nonseminomas often contain pluripotent embryonal carcinoma (EC) cells, the cancer stem cells (CSCs) of these tumors. We hypothesized that differentiation therapy, a treatment strategy which aims to induce differentiation of tumor-propagating CSCs to slow tumor growth, could effectively treat mixed nonseminomas without significant toxicity. The FDA-approved antipsychotic thioridazine and the agricultural antibiotic salinomycin are two drugs previously found to selectively target CSCs, and here we report that these agents differentiate EC cells in vitro and greatly reduce their tumorigenic potential in vivo. Using a novel transformed induced pluripotent stem cell allograft model and a human xenograft model, we show that thioridazine extends the survival of tumor-bearing mice and can reduce the number of pluripotent EC cells within tumors. These results suggest that thioridazine could be repurposed as an alternative TGCT treatment that avoids the toxicity of conventional chemotherapeutics.

Serum Lactate Dehydrogenase Isoenzyme 1 and Relapse in Patients with Nonseminomatous Testicular Germ Cell Tumors Clinical Stage I

2001 ◽  
Vol 40 (4) ◽  
pp. 536-540 ◽  
Author(s):  
Finn Edler von Eyben ◽  
Ebbe Lindegaard Madsen ◽  
Ole Blaabjerg ◽  
Per Hyltoft Petersen ◽  
Hans von der Maase ◽  
...  
Keyword(s):  
Lactate Dehydrogenase ◽  
Germ Cell ◽  
Clinical Stage ◽  
Germ Cell Tumors ◽  
Serum Lactate ◽  
Stage I ◽  
Serum Lactate Dehydrogenase ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell ◽  
Dehydrogenase Isoenzyme

Molecular Mechanisms of Resistance in Testicular Germ Cell Tumors - clinical Implications

2018 ◽  
Vol 18 (10) ◽  
pp. 967-978 ◽  
Author(s):  
Katarina Kalavska ◽  
Vincenza Conteduca ◽  
Ugo De Giorgi ◽  
Michal Mego
Keyword(s):  
Germ Cell ◽  
Molecular Mechanisms ◽  
Cisplatin Resistance ◽  
Apoptotic Cell ◽  
Germ Cell Tumors ◽  
Treatment Resistance ◽  
Experimental Models ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell ◽  
Repair Capacity

Testicular germ cell tumors (TGCTs) represent the most common malignancy in men aged 15-35. Due to these tumors’ biological and clinical characteristics, they can serve as an appropriate system for studying molecular mechanisms associated with cisplatin-based treatment resistance. This review describes treatment resistance from clinical and molecular viewpoints. Cisplatin resistance is determined by various biological mechanisms, including the modulation of the DNA repair capacity of cancer cells, alterations to apoptotic cell death pathways, deregulation of gene expression pathways, epigenetic alterations and insufficient DNA binding. Moreover, this review describes TGCTs as a model system that enables the study of the cellular features of cancer stem cells in metastatic process and describes experimental models that can be used to study treatment resistance in TGCTs. All of the abovementioned aspects may help to elucidate the molecular mechanisms underlying cisplatin resistance and may help to identify promising new therapeutic targets.

scholarly journals Teratomatous Elements in Orchiectomy Specimens Are Associated with a Reduced Relapse-Free Survival in Metastasized Testicular Germ Cell Tumors

2021 ◽  
pp. 1-7
Author(s):  
Pia Paffenholz ◽  
Tim Nestler ◽  
Yasmine Maatoug ◽  
Melanie von Brandenstein ◽  
Barbara Köditz ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumors ◽  
Retroperitoneal Lymph Node Dissection ◽  
Advanced Tumor Stage ◽  
Testicular Germ Cell Tumors ◽  
Relapse Free Survival ◽  
Testicular Germ Cell ◽  
Free Survival ◽  
Advanced Tumor ◽  
The Impact

<b><i>Introduction:</i></b> The impact of teratomatous elements in orchiectomy specimens of metastasized testicular germ cell tumors (TGCT) regarding oncological outcome is still unclear. <b><i>Methods:</i></b> We performed a retrospective analysis including 146 patients with metastasized TGCT analysing patient characteristics. <b><i>Results:</i></b> Twenty-six (18%) of all patients showed teratomatous elements in the orchiectomy specimens. TGCT with teratomatous elements showed a significantly higher frequency of clinical-stage 2C-3 disease (73 vs. 49%, <i>p</i> = 0.031), visceral metastases (58 vs. 32%, <i>p</i> = 0.015), and poor prognosis (<i>p</i> = 0.011) than TGCT without teratomatous elements. Teratoma-containing TGCT revealed a significantly higher rate of post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND, 54 vs. 32%, <i>p</i> = 0.041), with teratomatous elements being more often present in the PC-RPLND specimens (43 vs. 11%, <i>p</i> = 0.020) than nonteratoma-containing primaries. In the Kaplan-Meier estimates, the presence of teratomatous elements in orchiectomy specimens was associated with a significantly reduced relapse-free survival (RFS) (<i>p</i> = 0.049) during a median follow-up of 36 months (10–115.5). <b><i>Conclusions:</i></b> The presence of teratomatous elements in orchiectomy specimens is associated with an advanced tumor stage, worse treatment response as well as a reduced RFS in metastasized TGCT. Consequently, the presence of teratomatous elements might act as a reliable stratification tool for treatment decision in TGCT patients.

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